Oxidant injury may contribute to airways obstruction. We propose to test the hypothesis that there are two distinct responses which occur in the lung periphery following exposure to ozone. The first response involves more proximal small airways, is characterized by increased resistance to flow through those airways, is modulated through the parasympathetic system, and is associated with increased reactivity to histamine. In contract, the second response involves the more peripheral lung parenchyma, is characterized by increased resistance to flow through collateral channels, is mediated by humoral agents, and is associated with edema, decreased perfusion, and compromised metabolic function. Anesthetized dogs are to be studied. A fiberoptic bronchoscope is wedged into periphral airway so that it obstructs a sublobar segment of lung. Ozone (ranging from 0.1 to 2 ppm) is directed locally through the bronchoscope into the collaterally ventilated obstructed area. Responses of small airways, collateral channels and pulmonary blood vessels are monitored. Effects of ozone exposure on the responses to histamine, the uptake of amphetamine by the lung and the development of edema will be assessed. The role o the parasympathetic nervous system and the female sex hormones (progesterone) on these responses will be investigated. Inasmuch as acute responses of small airways and the periphery of the lung play a role in the development of chronic airflow limitation in man, results from these studies will provide insight into the pathophysiology of early airways obstruction as well as acute reactions of the lung.